73986-53-5

Usage

Uses

O-Desmethyl Tramadol, is a metabolite of Tramadol, an analgesic.

InChI:InChI=1/C15H23NO2/c1-16(2)11-13-6-3-4-9-15(13,18)12-7-5-8-14(17)10-12/h5,7-8,10,13,17-18H,3-4,6,9,11H2,1-2H3

Synthetic route

[2-(2,6-dichloroanilino)phenyl]acetic acid (15307-86-5) + O-desmethyltramadol (73986-53-5) → O-desmethyl-tramadol-diclofenac

Conditions	Yield
In isopropyl alcohol at 20℃; Product distribution / selectivity;	100%

O-desmethyltramadol (73986-53-5) + (S)-ibuprofen (51146-56-6) → O-desmethyl-tramadol-(S)-ibuprofen

Conditions	Yield
In toluene at 20℃; for 3h;	91%

3-acetyl-2-hydroxybenzoic acid (67127-78-0) + O-desmethyltramadol (73986-53-5) → O-desmethyl-tramadol-acetylsalicylic acid

Conditions	Yield
In chloroform at 20℃; Product distribution / selectivity;	88%

O-desmethyltramadol (73986-53-5) + triflusal (322-79-2) → O-desmethyl-tramadol-triflusal

Conditions	Yield
In ethyl acetate at 0 - 20℃; for 0.666667h; Product distribution / selectivity; Cooling with ice;	77%

O-desmethyltramadol (73986-53-5) + (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (22204-53-1) → O-desmethyl-tramadol-(S)-naproxen

Conditions	Yield
In chloroform Product distribution / selectivity; Heating;	66%

fluorobiprofen (5104-49-4) + O-desmethyltramadol (73986-53-5) → O-desmethyl-tramadol-flurbiprofen

Conditions	Yield
In acetic acid butyl ester Product distribution / selectivity;	65%

N-Boc-gabapentin (227626-60-0) + O-desmethyltramadol (73986-53-5) → (1R2R,1S2S)-3-(2-((dimethylamino)methyl)-1-hydroxycyclohexyl)phenyl 2-(1-((tert-butoxycarbonylamino)methyl)cyclohexyl)acetate (1345016-64-9)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 16h;	44%

Carbonyldiimidazole (64269-79-0) + ibuprofen (15687-27-1) + O-desmethyltramadol (73986-53-5) → 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl 2-(4-isobutyl-phenyl)-propionate (269079-66-5)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; dichloromethane; water; mineral oil
With sodium hydroxide In tetrahydrofuran; dichloromethane; water; mineral oil

Upstream product

• 36282-47-0 tramadol hydrochloride 
• 27203-92-5 cis-tramadol 
• 2914-77-4 tramadol 

Downstream Products

• 269079-66-5 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl 2-(4-isobutyl-phenyl)-propionate 
• 1345016-64-9 (1R₂R,1S₂S)-3-(2-((dimethylamino)methyl)-1-hydroxycyclohexyl)phenyl 2-(1-((tert-butoxycarbonylamino)methyl)cyclohexyl)acetate 
• 138853-75-5 3-<2-(e)-Dimethylaminomethyl-1(a)-hydroxycylohexyl>-phenyl-β-D-glucopyranuronsaeure 
• 16412-54-7 (+/-)-mono-O-demethyltramadol hydrochloride 
• 144830-14-8 (+)-O-Demethyltramadol 

Relevant academic research and scientific papers

A PROCESS FOR PREPARATION OF O-DESMETHYLTRAMADOL AND SALTS THEREOF

The present invention relates to a process of preparation of O-Desmethyl tramadol through potassium hydroxide mediated demethylation of Tramadol under phase transfer conditions.

Photocatalytic degradation and mineralization of tramadol pharmaceutical in aqueous TiO2 suspensions: Evaluation of kinetics, mechanisms and ecotoxicity

In the present study the transformation and mineralization of a common aquatic pollutant, Tramadol (TRA) was investigated for the first time by means of TiO2 photocatalysis. The degradation kinetics for both TRA and total organic carbon (TOC) followed apparent first-order model with rate constants of k = 15.3 10 min and k = 9.7 10 min and half lives (t) of 4.5 min and 71.4 min, respectively. The transformation products (TPs) of TRA, were identified by high resolution accurate mass liquid chromatography (HR-LC-MS) suggesting that hydroxylation, oxidation and dealkylation are the main transformation pathways. The reactions were found to occur mainly at the surface of the photocatalyst via surface-bound HO radicals rather than by free diffusion into the homogeneous phase. The potential risk of TRA and its TPs to aqueous organisms was investigated using Microtox bioassay before and during the process. The acute toxicity increased in the first stages and then decreased rapidly to very low values within 120 min of the photocatalytic treatment. The increase in the toxicity is associated with near additive or low synergistic effects between two TPs generated during the process i.e. N-desmethyl and N-oxide tramadol.

COMPOSITIONS AND METHODS FOR OVERCOMING RESISTANCE TO TRAMADOL

There is disclosed a composition for oral administration of O-desmethyltramadol. There is further disclosed a method for treating disorders modulated by at least opiate receptor activity or monoamine activity, including acute and chronic pain, comprising administering a pharmaceutical formulation comprising O-desmethyltramadol. Compositions and methods are also provided that are effective for overcoming resistance to tramadol in patients.